The Development of Digital Breast Tomosynthesis at Mass General: From Invention to Clinical Application

In 1978, Daniel B. Kopans, MD, was appointed head of the Xeroradiography Division at Massachusetts General Hospital. In addition to other soft tissue imaging, the division performed mammograms for eight women each day (2,000 each year) using the xeroradiographic technique. Mammography screening was in its infancy, but Dr. Kopans helped to develop this new field of "Breast Imaging" (1). The Division of Breast Imaging at Mass General now cares for more than 35,000 women each year and has led the development of Breast Imaging as a radiologic sub-specialty.

Since the inception of mammography, the ability to detect breast cancer on 2-dimensional (2D) mammograms has been compromised by superimposed normal breast tissues hiding many small cancers. The standard mammogram is like a book with clear pages. You can hold the book up to the light and look through it, but the words are superimposed one on the other making it difficult to read.

Dr. Kopans sought a way to look at each page, individually, to allow radiologists to uncover hidden cancers. Computed tomography and other methods to accomplish this require high doses of radiation. In 1978, reading about a technique called tomosynthesis, Dr. Kopans realized that this could be the solution to the problem. A few low dose x-ray images taken from different directions would allow him to synthesize as many "pages" through the breast as were needed. Unfortunately, he had to wait almost 15 years for the development of digital detectors and computers powerful enough to enable breast imaging using tomosynthesis.

In 1992, while helping to develop digital detectors for mammography, Dr. Kopans set a goal for the Mass General Division of Breast Imaging to develop tomosynthesis of the breast. In 1996, Mass General physicist Loren Niklason, PhD, Laura E. Niklason, MD, PhD and Dr. Kopans filed a patent entitled "Tomosynthesis System for Breast Imaging," which described a digital breast tomosynthesis (DBT) system that collected digital images from X-rays passing through the breast from a tube that moved above the breast (2). These DBT projection images from the system allowed the creation of the "pages" through the breast that Dr. Kopans had envisioned. The patent was approved in 1999 (#5872828). Obtaining a grant from the U.S. Department of Defense, Mass General sub-contracted to General Electric to build the first DBT prototype.

Using the this prototype, the Mass General team obtained a whole breast DBT study of the first volunteer in 1999. To our knowledge, this was the first DBT exam ever acquired. Subsequent research at Mass General involving thousands of additional volunteers showed that DBT could find cancers that were not visible on standard 2D mammography (Figure 1). As a further benefit, because it eliminated the superposition of normal tissues that could simulate a cancer, DBT also reduced the "false positive" recall rate (3,4). Mass General subsequently licensed the DBT patent to General Electric.

Mammography screening was introduced in the US in the mid-1980s. Owing to earlier detection and improvements in therapy, the death rate from breast cancer began to fall in 1990 for the first time in 50 years (5,6). There are now 35% fewer women who die each year from breast cancer than would have died had screening not been introduced (7,8,9,10,11,12,13,14,15,16,17,18,19,20).

Therapy has improved, but the most lives are saved when breast cancers are treated earlier. Recognizing that 2D mammography was not the ultimate answer to detecting breast cancer, Dr. Kopans pursued DBT as a major improvement. Numerous studies have now shown that DBT can find more small breast cancers that are missed on standard 2D mammography (21,22,23,24,25,26,27,28,29,30) while reducing the recall rate from screening (3,4,31,32,33,34).

References

  1. Kopans DB, Meyer JE, Sadowsky N. Breast Imaging. N Engl J Med 1984; 310:960-967.
  2. Niklason LT, Christian BT, Niklason LE, Kopans DB, Castleberry DE, Opsahl-Ong BH, Landberg CE, Slanetz PJ, Giardino AA, Moore R, Albagli D, DeJule MC, Fitzgerald PF, Fobare DF, Giambattista BW, Kwasnick RF, Liu J, Lubowski SJ, Possin GE, Richotte JF, Wei CY, Wirth RF. Digital tomosynthesis in breast imaging. Radiology. 1997 Nov;205(2):399-406.
  3. Rafferty EA, Kopans DB, Georgian-Smith D, et al. Evaluation of the call-back rate for screening mammography using full-field digital tomosynthesis versus conventional film screen mammography [abstract]. In: Abstracts of the 103rd Annual Meeting of the American Roentgen Ray Society. San Diego (CA), May 4–9, 2003.
  4. Moore, R.H., Levy, A., Stewart, A. et al, Reading behavior for screening digital breast tomosynthesis (DBT) compared to conventional 2D mammography (CM). in: RNS, ; 2006:335 (abstract SSG01-05).
  5. Kopans DB. Beyond randomized controlled trials: organized mammographic screening substantially reduces breast carcinoma mortality. Cancer. 2002;94:580-1
  6. Kopans DB. The 2009 US Preventive Services Task Force (USPSTF) Guidelines are not Supported by Science: The Scientific Support for Mammography Screening. Radiologic Clinics of North America Volume 48, Issue 5, Pages 843-857
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  9. Otto SJ , Fracheboud J, Looman CWN, Broeders MJM, Boer R, Hendriks JNHCL, Verbeek ALM, de Koning HJ, and the National Evaluation Team for Breast Cancer Screening* Initiation of population-based mammography screening in Dutch municipalities and effect on breast-cancer mortality: a systematic review Lancet 2003;361:411-417.
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  11. Otto SJ, Fracheboud J, Verbeek ALM, Boer R, Reijerink-Verheij JCIY, Otten JDM,. Broeders MJM, de Koning HJ, and for the National Evaluation Team for Breast Cancer Screening. Mammography Screening and Risk of Breast Cancer Death: A Population-Based Case–Control Study. Cancer Epidemiol Biomarkers Prev. Published OnlineFirst December 6, 2011; doi: 10.1158/1055-9965.EPI-11-0476
  12. Swedish Organised Service Screening Evaluation Group. Reduction in breast cancer mortality from organized service screening with mammography: 1. Further confirmation with extended data. Cancer Epidemiol Biomarkers Prev. 2006;15:45-51.
  13. Hellquist BN, Duffy SW, Abdsaleh S, Björneld L, Bordás P, Tabár L, Viták B,Zackrisson S, Nyström L, Jonsson H. Effectiveness of population-based servicescreening with mammography for women ages 40 to 49 years: evaluation of theSwedish Mammography Screening in Young Women (SCRY) cohort. Cancer. 2010 Sep 29.
  14. Coldman A, Phillips N, Warren L, Kan L. Breast cancer mortality afterscreening mammography in British Columbia women. Int J Cancer. 2007 Mar1;120(5):1076-80.
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  17. Paap E, Holland R, den Heeten GJ, et al. A remarkable reduction of breast cancer deaths in screened versus unscreened women: a case-referent study. Cancer Causes Control 2010; 21: 1569-1573
  18. Hofvind S, Ursin G, Tretli S, Sebuødegård S, Møller B. Breast cancer mortality in participants of the Norwegian Breast Cancer Screening Program. Cancer. 2013 Sep 1;119(17):3106-12
  19. Coldman A, Phillips N, Wilson C, Decker K, Chiarelli AM, Brisson J, Zhang B, Payne J, Doyle G, Ahmad R. Pan-canadian study of mammography screening and mortality from breast cancer. J Natl Cancer Inst. 2014 Oct 1;106(11).
  20. http://seer.cancer.gov/csr/1975_2011/browse_csr.php?sectionSEL=4&pageSEL=sect_04_table.06.html last accessed 3/26/2015
  21. Niklason LT, Christian BT, Niklason LE, Kopans DB, Castleberry DE, Opsahl-Ong BH, Landberg CE, Slanetz PJ, Giardino AA, Moore R, Albagli D, DeJule MC, Fitzgerald PF, Fobare DF, Giambattista BW, Kwasnick RF, Liu J, Lubowski SJ, Possin GE, Richotte JF, Wei CY, Wirth RF. Digital tomosynthesis in breast imaging. Radiology. 1997 Nov;205(2):399-406. PubMed PMID: 9356620.
  22. Friedewald SM, Rafferty EA, Rose SL, Durand MA, Plecha DM, Greenberg JS, Hayes MK, Copit DS, Carlson KL, Cink TM, Barke LD, Greer LN, Miller DP, Conant EF. Breast cancer screening using tomosynthesis in combination with digital mammography. JAMA. 2014 Jun 25;311(24):2499-507. doi: 10.1001/jama.2014.6095. PubMed PMID: 25058084.
  23. Rose SL, Tidwell AL, Ice MF, Nordmann AS, Sexton R Jr, Song R. A Reader Study Comparing Prospective Tomosynthesis Interpretations with Retrospective Readings of the Corresponding FFDM Examinations. Acad Radiol. 2014 Sep;21(9):1204-10. doi: 10.1016/j.acra.2014.04.008. PubMed PMID: 25107868.
  24. Greenberg JS, Javitt MC, Katzen J, Michael S, Holland AE. Clinical Performance Metrics of 3D Digital Breast Tomosynthesis Compared With 2D Digital Mammography for Breast Cancer Screening in Community Practice. AJR Am J Roentgenol. 2014 Jun 11:1-7.
  25. Skaane P, Bandos AI, Gullien R, et al. Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-based screening program. Radiology 2013; 267:47–56
  26. Ciatto S, Houssami N, Bernardi D, et al. Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening (STORM): a prospective comparison study. Lancet Oncol 2013; 14:583–589
  27. Gennaro G, Hendrick RE, Toledano A, Paquelet JR, Bezzon E, Chersevani R, di Maggio C, La Grassa M, Pescarini L, Polico I, Proietti A, Baldan E, Pomerri F, Muzzio PC. Combination of one-view digital breast tomosynthesis with one-view digital mammography versus standard two-view digital mammography: per lesion analysis. Eur Radiol. 2013 Aug;23(8):2087-94. doi: 10.1007/s00330-013-2831-0. Epub 2013 Apr 26. PubMed PMID: 23620367
  28. Gennaro G, Hendrick RE, Ruppel P, et al. Performance comparison of single-view digital breast tomosynthesis plus single-view digital mammography with two-view digital mammography. Eur Radiol 2013; 23:664–672
  29. Rafferty EA, Park JM, Philpotts LE, Poplack SP, Sumkin JH, Halpern EF, Niklaso, LT. Diagnostic Accuracy and Recall Rates for Digital Mammography and Digital Mammography Combined With One-View and Two-View Tomosynthesis: Results of an Enriched Reader Study. AJR 2014; 202:273–281.
  30. Friedewald SM, Rafferty EA, Rose SL, Durand MA, Plecha DM, Greenberg JS, Hayes MK, Copit DS, Carlson KL, Cink TM, Barke LD, Greer LN, Miller DP, Conant EF. Breast cancer screening using tomosynthesis in combination with digital mammography. JAMA. 2014 Jun 25;311(24):2499-507. doi: 10.1001/jama.2014.6095. PubMed PMID: 25058084
  31. Niklason LT, Kopans DB, Hamberg LM. Digital breast imaging: tomosynthesis and digital subtraction mammography. Breast Dis. 1998 Aug;10(3-4):151-64
  32. Rafferty EA, Kopans DB, Georgian-Smith D, et al. Comparison of full-field digital tomosynthesis and conventional two view film screen mammography in lesion detection and assessment of lesion conspicuity [abstract]. In: Abstracts of the 103rd Annual Meeting of the American Roentgen Ray Society. San Diego (CA), May 4–9, 2003
  33. Rafferty EA, Wu T, Moore RH, Kopans DB, et al. Optimization of image acquisition and display algorithms to enhance visualization of microcalcifications during digital breast tomosynthesis [abstract E16–499]. In: Abstracts of the 89th Scientific Assembly and Annual Meeting of the Radiological Society of North America. Chicago, November 30–December 5, 2003.
  34. Rafferty EA, Georgian-Smith D, Kopans DB, et al. Comparison of full-field digital tomosynthesis with two view conventional film screen mammography in the prediction of lesion malignancy [abstract A14–135]. In: Abstracts of the 88th Scientific Assembly and Annual Meeting of the Radiological Society of North America. Chicago, December 1–6, 2002

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